注射用雷替曲塞在结、直肠肿瘤患者体内的药动学  

Pharmacokinetics of raltitrexed for injection in patients with colorectal carcinoma

作　　者：阎昭[1] 薛津怀[1] 朱仲玲 

机构地区：[1]天津医科大学附属肿瘤医院国家药品临床研究机构天津市肿瘤防治重点实验室,天津300060

出　　处：《中国医院药学杂志》2010年第9期749-752,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:建立人血浆中雷替曲塞浓度的HPLC检测方法,评价注射用雷替曲塞在结、直肠肿瘤患者体内的药动学特征。方法:采用HPLCC18色谱柱(250mm×4.6mm,5μm);流动相为乙腈-磷酸盐缓冲液(19:81,pH2.65);流速1.0mL.min-1;柱温30℃;紫外检测波长348nm。8名肿瘤受试者单剂量静脉滴注雷替曲塞注射液3mg.m-2,用HPLC法测定血浆中雷替曲塞的浓度,并计算药动学参数。结果:该测定方法浓度范围在2.5～2000μg.L-1线性关系良好,得回归方程为Y=280.98X+849.82,r=0.9999(n=3)。最低检测限为2.5μg.L-1,提取回收率为85%～105%,批间差和批内差RSD均<15%。肿瘤受试者静脉滴注雷替曲塞后,药物达峰时间(tmax)均在滴注结束时;药峰浓度(Cmax)为(852.2±286.1)μg.L-1;AUC(0-t)为(721.3±159.4)μg.L-1.h;终末半衰期(t1/2z)为(27.4±38.5)h;血浆清除率(CLz)为(3.6±1.2)L.h.m-2;表观分布容积(Vz)为(99.6±86.4)L.m-2。结论:国产注射用雷替曲塞在结、直肠肿瘤受试者体内,主要药动学参数与国外研究结果相近,没有明显种族差异。OBJECTIVE To establish HPLC method for raltitrexed in human plasma and to study the pharmacokinetics of rahitrexed for injection in patients with colorectal carcinomaMETHODS HPLC analysis was performed using a Kromasil col- umn （250 mm × 4. 6 mm,5 um）; the mobile phase consisted of acetonitrile-phosphate buffer solution （19：81, pH = 2. 65）, the flow rate was 1.0 mL.min^-1 , the temperature of column was about 30℃ and determined at UV （2 = 348 nm）. Eight tumor patients for single-dose pharmacokinetic study received rahitrexrd of 3 mg/m^2 , the plasma concentrations were determined by HPLC method and DAS 2. 0 was applied to assess the plasma concentration time data. RESULTS The calibration curve is linear in the rang of 2.5 -2 000ug·L^-1 ,y= 280. 98X＋ 849. 82,r= 0. 999 9（n = 3）. The minimal detectable drug concentration was 2. 5 ng·mL^-1, the average recovery rate was 85%- 105%, the inter day and intra-day validation were less than 15%. Tumor patients for single-dose pharmacokinetic study, tmax were 0. 25 h; Cmax were（852. 2 ± 296. 1 ）ug·L^-1 ; AUC（0-t）） were （721.3±159. 4） ug·L^-1· h;t1/2x were （27.4 ± 38. 5）h; CLz were （3.6 ±1. 2）L·h-m^-2 and Vz were （99. 6 ± 86.4）L·m^-2. CONCLUSION The main pharmacokinetic parameters of rahitrexed was kindred with foreign literatures,there was no significant difference between different races.

关 键 词：雷替曲塞 高效液相色谱法 药动学 

分 类 号：R969.1[医药卫生—药理学]